Derivatives of certain geranyl phenyl ethers

ABSTRACT

Compounds having the formula +q,10  IN WHICH R is hydrogen, lower alkyl, lower alkenyl, lower alkoxy, halogen, nitro; or lower alkylthio; X is chlorine or bromine; A and B are each hydrogen, together form an epoxide link or together form a bond; the use of these compounds in controlling insects; and a method of preparing these compounds.

This is a division of application Ser. No. 198,018 filed Nov. 4, 1971,now abandoned.

This invention relates to the use of certain novel chemical compounds incontrolling insects, more particularly, the chemical compounds arecertain derivatives of phenyl geranyl ethers. The invention also relatesto a method of preparing the compounds.

It has been found that there is a class of compounds which acts in adifferent manner on insects than presently used insecticides and exertsa disrupting influence upon the normal development of insects. Suchcompounds impede the metamorphosis of the normal pupation of pestinsects and result in the formation of numbers of the treated specieswhich are not-viable or sterile. This ultimately leads, indirectly atleast, to the destruction of a pest population.

The compounds of the present invention are believed to have the furtheradvantages that they are non-toxic to warm-blooded animals and highlyeffective to control insects at low dosages. It is also hoped that itwill be more difficult for insects to develop resistance against thesecompounds.

One embodiment of the present invention is concerned with novelpesticidal compositions.

In another embodiment, the invention is concerned with the activepesticidal component of such compositions.

In still another embodiment, the invention is concerned with a processfor controlling insects by hindering or impeding the metamorphosis andreproduction of the insects.

And in another embodiment, the invention is concerned with a process forpreparing certain epoxidized compounds.

The compounds of the present invention that are useful in controllinginsects are those having the formula ##SPC2##

In which R is hydrogen; halogen; lower alkyl having 1 to 6 carbon atoms,preferably 1 to 4 carbon atoms; lower alkoxy having 1 to 4 carbon atoms,preferably 1 to 2 carbon atoms; lower alkenyl, having 2 to 6 carbonatoms, preferably 3 to 4 carbon atoms; lower alkylthio having 1 to 4carbon atoms, preferably 1 to 2 carbon atoms, or nitro, most preferably,R is in the para-position; X is chlorine or bromine; and A and B areeach hydrogen, together form an epoxide link or together form a bond.The term halogen covers chlorine, bromine, iodine and fluorine.

Carbon atoms, joined to two or less hydrogen atoms, occupy each angle inthe backbone of the compound represented by the above formula unlessotherwise specified. Letters at the terminals and branches have beenused to show the attached groups.

The certain halogenating agents recited herein are t-alkyl hypochlorite,preferably t-butyl hypochlorite; t-alkyl hypobromite, preferably t-butylhypobromite; HOCl, HOBr; or N-bromoimides, preferablyN-bromosuccinimide.

As indicated heretofore, the above compounds are useful in impeding themetamorphosis and/or the reproduction of insects. The activity of thecompounds is such that insects at any stage of their development can beeffectively treated therewith.

Reaction No. 1

The compound having the formula ##SPC3##

in which R and X are defined can be prepared by the following reaction:##SPC4##

in which R is as defined.

Preferably, reaction number 1 is carried out in a solvent such asmethylene chloride, preferably the certain halogenating agent is addedslowly with stirring and at a temperature sufficient to give acontrolled reaction, such as about 0° C. to about 10° C. Preferablyreaction number 1 is carried out using about equal mole amounts of thereactants, or with a slight excess of the halogenating agent. Thereaction product is recovered by conventional means.

Reaction No. 2

The compounds having the formula ##SPC5##

in which R and X are as defined, can be prepared by the followingreaction: ##SPC6##

in which R and X are as defined.

Preferably, reaction number 2 is carried out in a solvent such asmethylene chloride, preferably the epoxidizing agent is added slowlywith stirring at a temperature sufficient to give a controlled reaction,such as about 5° C. to about 10° C. Preferably reaction number 2 iscarried out using about equal mole amounts of the reactants, or with aslight excess of the epoxidizing agent. The reaction product isrecovered by conventional means.

The epoxidizing agents are well-known to those skilled in the art andinclude such materials as metachloroperbenzoic acid. References are madeto Kirk-Othmer Encyclopedia of Chemical Technology, 2nd Edition, 1965,Vol. 8, pages 238-244, for a discussion of various types of epoxidizingagents.

Reaction No. 3

Compounds having the formula ##SPC7## in which R and X are as defined,can be prepared by the following reactions: ##SPC8##

in which R is as defined.

Preferably, reaction number 3 is carried out in a solvent such asmethylene, chloride, preferably the certain halogenating agent is addedslowly with stirring and at a temperature sufficient to give acontrolled reaction, such as about 0° C. to about 10° C. Preferablyreaction number 3 is carried out using about equal mole amounts of thereactants, or with a slight excess of the halogenating agent. Thereaction product is recovered by conventional means.

A process of this invention is one for preparing a compound of theformula: ##SPC9##

in which R is hydrogen; halogen, lower alkyl having 1 to 6 carbon atoms;lower alkoxy having 1 to 4 carbon atoms; lower alkenyl having 2 to 6carbon atoms; lower alkylthio having 1 to 4 carbon atoms; or nitro; andC and D are each hydrogen, or together form a bond comprising the stepof reacting a compound of the formula: ##SPC10##

in which R, C and D are as defined with t-butyl hypochlorite, or HOCl.

Preferably, the reaction is carried out in a solvent such as methylenechloride, preferably the recited chlorinating agent is added slowly withstirring and at a temperature sufficient to give a controlled reaction,such as about 0° C. to about 10° C. Preferably the reaction is carriedout using about equal mole amounts of the reactants or with a slightexcess of the chlorinating agent. The reaction product is recovered byconventional means. Another process of this invention is one forpreparing a compound of the formula: ##SPC11##

in which R is hydrogen; halogen; lower alkyl having 1 to 6 carbon atoms;lower alkoxy having 1 to 4 carbon atoms; lower alkenyl having 2 to 6carbon atoms; lower alkylthio having 1 to 4 carbon atoms; or nitro; andC and D are each hydrogen, or together form a bond comprising the stepof reacting a compound of the formula: ##SPC12##

in which R, C and D are as defined with t-butyl hypobromite HOBr orN-bromosuccinimide.

Preferably the reaction is carried out in a solvent such as methylenechlorine, preferably the brominating agent is added slowly with stirringand at a temperature sufficient to give a reaction is carried out usingabout equal mole amounts of the reactants, or with a slight excess ofthe brominating agent. The reaction product is recovered by conventionalmeans. Preparation of the compounds of this invention is illustrated bythe following specific examples.

EXAMPLE I 1-(4'-ethyl) phenoxy-3,7-dimethyl-6-chloro-2,7-octadiene##SPC13##

2.58 g. (0.01 mole) of a compound of the formula ##SPC14##

is dissolved in 25 ml. CH₂ Cl₂ and cooled in an ice bath. Slowly 1.1 g.(0.01 mole) t-butylhypochlorite in 10 ml. CH₂ Cl₂ is added dropwise at atemperature of 0°-5° C. The mixture is stirred in an ice bath for 1/2hour and at room temperature for 1 hour and allowed to stand overnight.The reaction product is worked up by adding 15 ml. CH₂ Cl₂ and themixture is washed with water, with 10% NaHCO₃ twice, dried over MgSO₄filtered and stripped to yield 2.3 g. of the desired product, N_(D) ³⁰1.5200. The structure is confirmed by I.R., n.m.r. and massspectroscopy.

EXAMPLE II 1-(4'-ethyl) phenoxy-3,7-dimethyl-6-chloro-2,7-octadiene##SPC15##

12.5 ml. of a 5.5% solution of NaOCl are stirred and cooled in an icebath. A mixture of 2.58 gr. (0.01 mole) of a compound of the formula##SPC16##

and 0.7 gr. CH₃ COOH acetic acid glacial are added at once. The aceticacid and the NaOCl react to form HCCl in situ. Temperature goes from 8°C. to 26° C. The mixture is stirred for 1/2 hour. The reaction productis recovered by adding CH₂ Cl₂, separating the organic layer. This iswashed with 10% NaHCO₃ solution, dried over MgSO₄, filtered and strippedto yield 2.1 gr. of the desired product N_(D) ³⁰ 1.5220. The structureis confirmed by I.R. and n.m.r. spectroscopy.

EXAMPLE III 1-(4'-ethyl) phenoxy-3,7-dimethyl-6-bromo-2,7-octadiene##SPC17##

1.3 gr. (0.005 mole) of a compound of the formula ##SPC18##

is dissolved in 15 ml. 1,2-dimethoxyethane and 1.8 gr. (0.015 mole)N-bromosuccinimide are mixed at a temperature of 0° C. to 5° C. andstirred at room temperature overnight. The mixture is evaporated todryness with a water aspirator. 50 ml. CCl₄ is added and the mixturestirred. A solid form is removed by filtration. The solid is washed withCCl₄. The organic layers are combined, washed twice with water, driedover MgSO₄, filtered and stripped. 1.9 gr. of the desired product isobtained, N_(D) ³⁰ 1.4570. I.R. and n.m.r. spectroscopy confirm thestructure.

EXAMPLE IV 3,7-dimethyl-6-chloro-1-p-ethylphenoxy-2,3-epoxy-7-octene##SPC19##

1.17 gr. (0.004 mole) of the reaction product of Example 1 is dissolvedin 10 ml. CH₂ Cl₂, 0.004 mole of m-chloroperbenzoic acid solution in CH₂Cl₂ are slowly added dropwise at 0° to 5° C. temperature: The mixture isstirred at room temperature overnight, then washed with 10 ml. NaHCO₃three times, dried over MgSO₄, filtered and stripped to yield 0.9 gramsof the desired product N_(D) ³⁰ 1.5160. The structure is confirmed byI.R., n.m.r. mass spectroscopy.

The following is a table of certain selected compounds that arepreparable according to the procedures described hereto. Compoundnumbers are assigned to each conmpound and are used throughout theremainder of the specification.

                  TABLE I                                                         ______________________________________                                         ##STR1##                                                                     COM-                                                                          POUND                                                                         NUMBER  R.sup.1                                                                              R.sup.2                                                                              X   A & B  R                                            ______________________________________                                         1      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-CH.sub.3 S                                  2      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-C.sub.2 H.sub.5                             3      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   4-C.sub.2 H.sub.5                             4      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   H                                             5      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-CH.sub.3                                    6      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   4-i-C.sub.3 H.sub.7                           7      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-NO.sub.2                                    8      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   3-Cl                                          9      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   4-Cl                                         10      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-Br                                         11      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-I                                          12      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   4-F                                          13      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-CN                                         14      CH.sub.3                                                                             CH.sub. 3                                                                            Cl  bond   3-CH.sub.3 O                                 15      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   4-CH.sub.3 O                                 16      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-C.sub.2 H.sub.5 O                          17      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   4-n-C.sub.4 H.sub.9                          18      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   4-CH.sub.3 CHCH                              19      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-CH.sub.3 CH.sub.2 CH(CH.sub.3)             20      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   4-n-C.sub.3 H.sub.7                          21      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   3-C.sub.2 H.sub.5                            22      CH.sub.3                                                                             CH.sub.3                                                                             Br  bond   3-C.sub.2 H.sub.5                            23      CH.sub.3                                                                             CH.sub.3                                                                             Cl  bond   4-sec.-C.sub.4 H.sub.9                       24      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-C.sub.2 H.sub.5                            25      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              H                                            26      CH.sub.3                                                                             CH.sub.3                                                                             Br  epoxide                                                                              4-CH.sub.3                                   27      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-i-C.sub.3 H.sub.7                          28      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-NO.sub.2                                   29      CH.sub.3                                                                             CH.sub.3                                                                             Br  epoxide                                                                              3-Cl                                         30      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-Cl                                         31      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-Br                                         32      CH.sub.3                                                                             CH.sub.3                                                                             Br  epoxide                                                                              4-I                                          33      CH.sub.3                                                                             CH.sub. 3                                                                            Cl  epoxide                                                                              4-F                                          34      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-CN                                         35      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              3-CH.sub.3 O                                 36      CH.sub.3                                                                             CH.sub.3                                                                             Br  epoxide                                                                              4-CH.sub.3 O                                 37      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-C.sub.2 H.sub.5 O                          38      CH.sub.3                                                                             CH.sub.3                                                                             Br  epoxide                                                                              4-n-C.sub.4 H.sub.9                          39      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-CH.sub.3 S                                 40      CH.sub.3                                                                             CH.sub.3                                                                             Br  epoxide                                                                              4-CH.sub.3 CHCH                              41      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-CH.sub.3 CH.sub.2 CH(CH.sub.3)             42      CH.sub.3                                                                             CH.sub.3                                                                             Br  epoxide                                                                              4-n-C.sub.3 H.sub.7                          43      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              3-C.sub.2 H.sub.5                            44      CH.sub.3                                                                             CH.sub.3                                                                             Br  epoxide                                                                              3-C.sub.2 H.sub.5                            45      CH.sub.3                                                                             CH.sub.3                                                                             Cl  epoxide                                                                              4-sec.-C.sub.4 H.sub.9                       46      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      H                                            47      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-CH.sub.3                                   48      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      4-i-C.sub.3 H.sub.7                          49      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-NO.sub.2                                   50      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      3-Cl                                         51      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      4-Cl                                         52      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-Br                                         53      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-I                                          54      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      4-F                                          55      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-CN                                         56      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      3-CH.sub.3 O                                 57      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      4-CH.sub.3 O                                 58      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-C.sub.2 H.sub.5 O                          59      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      4-n-C.sub.4 H.sub.9                          60      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-CH.sub.3 S                                 61      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-C.sub.2 H.sub.5                            62      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      4-C.sub.2 H.sub.5                            63      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      4-CH.sub.3 CHCH                              64      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-CH.sub.3 CH.sub.2 CH(CH.sub.3)             65      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      4-n-C.sub.3 H.sub.7                          66      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      3-C.sub.2 H.sub.5                            67      CH.sub.3                                                                             CH.sub.3                                                                             Br  H      3-C.sub.2 H.sub.5                            68      CH.sub.3                                                                             CH.sub.3                                                                             Cl  H      4-sec.-C.sub.4 H.sub.9                       ______________________________________                                    

INSECTICIDAL EVALUATION TEST

The degree of activity of a candidate compound to hinder or impede themetamorphosis of insects is measured by treating the penultimate larvalstage of a representative insect with the compound and examining itafter its last molt toward the adult form for retention of immaturefeatures.

Specifically, yellow mealworm, Tenebrio molitor, L., larvae aremaintained at 28° C. and 40% humidity on a diet of bran flakes. Prepupaecare collected from the culture and kept in separate containers. Thepupae collected once daily, are 1-25 hours old at the time of treatment.By means of a syringe, suitable amounts of candidate compounds in 0.5 or1.0 μ of acetone are applied to the ventor of Tenebrio molitor, L.pupae. Treated pupae are maintained at 28° C. and 40% humidity until theadults emerged (usually within 6-8 days). Emerged adults are graded aspositive, negative, or dead. To be considered a positive response, thepresence of typical pupal cuticle, urogomphi, gin trap, and abnormalwings, etc., are required. For each test, 2 groups of 20 pupae were usedand the averaged results were reported.

The dose of a candidate compound per pupa that is needed to kill or givea positive response in the above insecticidal evaluation test for 10 ofthe 20 pupae is determined. Table II shows these doses under the columnED₅₀.

                  TABLE II                                                        ______________________________________                                        COMPOUND                                                                      NUMBER           ED.sub.50 -μg/pupa                                        ______________________________________                                        1                0.3                                                          2                0.1                                                          3                0.5                                                          24                0.03                                                        ______________________________________                                    

The compounds of this invention are generally embodied into a formsuitable for convenient application. For example, the compounds can beembodied into pesticidal composition which are provided in the form ofemulsions, suspensions, solutions, dusts, and aerosol sprays. Ingeneral, such compositions will contain, in addition to the activecompound, the adjuvants which are found normally in pesticidepreparations. In these compositions, the active compounds of thisinvention can be employed as the sole pesticide component or they can beused in admixture with other compounds having similar utility. Thepesticide compositions of this invention can contain, as adjuvants,organic solvents, such as sesame oil, xylene range solvents, heavypetroleum, etc.; water; emulsifying agents; surface active agents; talc;pyrophyllite; diatomite; gypsum; clays, propelants, such asdichlorodifluoromethane, etc. If desired, however, the active compoundscan be applied directly to feedstuffs, seeds, etc. upon which the pestsfeed. When applied in such a manner, it will be advantageous to use acompound which is not volatile. In connection with the activity of thepresently disclosed pesticidal compounds, it should be fully understoodthat it is not necessary that they be active as such. The purposes ofthis invention will be fully served if the compound is rendered activeby external influences, such as light or by some physiological actionwhich occurs when the compound is ingested into the body of the pest.

The precise manner in which the pesticidal compositions of thisinvention are used in any particular instance will be readily apparentto a person skilled in the art. Generally, the active pesticide compoundwill be embodied in the form of a liquid composition, for example, anemulsion, suspension, or aerosol spray. While the concentration of theactive pesticide in the present compositions can vary within rather widelimits, ordinarily the pesticide compound will comprise not more about15.0% by weight of the composition. Preferably, however, the pesticidecompositions of this invention will be in the form of solutions orsuspensions containing about 0.1 to 1.0% weight of the active pesticidecompound.

What is claimed:
 1. A compound of the formula ##SPC20##in which R islower alkylthio having 1 to 4 carbon atoms; X is chlorine or bromine;and A and B together form a bond.
 2. The compound of claim 1 in which Xis chlorine; R is lower alkylthio having 1 to 2 carbon atoms.
 3. Thecompound of claim 2 in which R is 4-methylthio.